Efficacy and Safety Study of Pregabalin in the Treatment of Pain on Walking in Patients With Diabetic Peripheral Neuropathy (DPN)

• Sponsor: Pfizer's Upjohn has merged with Mylan to form Viatris Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01474772
• Collaborator: (none)
• Enrollment: 217
• Locations: 45
• Arms: 2
• Duration (Months): 21
• Patients Per Site: 4.8
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The intent of this study is to treat subjects with painful Diabetic Peripheral Neuropathy (DPN) who also have pain on walking and to determine whether or not pregabalin demonstrates improvement relative to placebo on the following: reducing DPN pain, reducing pain on walking, and providing other benefits associated with daily activities and quality of life.

Condition or Disease	Intervention/Treatment	Phase
Diabetic Peripheral Neuropathy	Drug: Pregabalin; Other: placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 217 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase 3b Multicenter, Double-blind, Randomized, Placebo-controlled Cross-over Efficacy And Safety Study Of Pregabalin In The Treatment Of Patients With Painful Diabetic Peripheral Neuropathy And Pain On Walking
• Study Start Date: Oct 1, 2011
• Actual Primary Completion Date: Jul 1, 2013
• Actual Study Completion Date: Jul 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Pregabain	Drug: Pregabalin; 150-300 mg/day given in 3 divided doses as capsules; Other Names: Lyrica
Placebo Comparator: Placebo	Other: placebo; matching placebo capsules given in 3 divided doses

Outcome Measures

Primary Outcome Measures

1. Average Diabetic Peripheral Neuropathy (DPN) Pain Based on a Numeric Rating Scale (NRS) Over the Last 7 Days of Each Treatment Period (Week 6 of Each Treatment Period) [End of Period (includes both Visits 6 and 11)]

   The daily pain diary consisted of an 11-point numeric scale ranging from 0 ("no pain") to 10 ("worst possible pain"). Participants described their pain during the past 24 hours by having chosen the appropriate number between 0 and 10. Self-assessment was performed daily each evening before bedtime (6.00 pm to midnight) on the telephone via Interactive Voice Recognition System (IVRS). The endpoint mean pain score was defined as the mean of the last 7 daily diary pain ratings while taking study medication in each treatment period - Period 1 and Period 2, respectively. A rating of 1 - 3 was considered as mild pain; 4 - 6 as moderate pain; and 7 - 10 as severe pain.

2. DPN Pain on Walking Based on a 11-point NRS of Each Treatment Period (Week 6 of Each Treatment Period) [End of Period (includes both Visits 6 and 11)]

   The post-test DPN pain on walking NRS consisted of an 11-point numeric scale ranging from 0 ("no pain") to 10 ("worst possible pain"). Participants described their DPN pain in their legs and/or feet while walking during the 50-foot walk test by choosing the appropriate number between 0 and 10. The post-test DPN pain on walking NRS was completed by the participant using paper-pen administration immediately after completing the 50-foot walk test at the end of each treatment period - Period 1 and Period 2, respectively. A rating of 1 - 3 was considered as mild pain; 4 - 6 as moderate pain; and 7 - 10 as severe pain.

Secondary Outcome Measures

1. Percentage of Participants Achieving 30% Reduction in Mean DPN Pain Score From Baseline at the End of Each Treatment Period (Week 6 of Each Treatment Period) [End of Period (includes both Visits 6 and 11)]

   The daily pain diary consisted of an 11-point numeric scale ranging from 0 ("no pain") to 10 ("worst possible pain"). Participants described their pain during the past 24 hours by having chosen the appropriate number between 0 and 10. Self-assessment was performed daily each evening before bedtime (6.00 pm to midnight) on the telephone via IVRS. The endpoint mean pain score was defined as the mean of the last 7 daily diary pain ratings while taking study medication in each treatment period - Period 1 and Period 2, respectively. A rating of 1 - 3 was considered as mild pain; 4 - 6 as moderate pain; and 7 - 10 as severe pain.

2. Percentage of Participants Achieving 50% Reduction in Mean DPN Pain Score From Baseline at the End of Each Treatment Period (Week 6 of Each Treatment Period) [End of Period (includes both Visits 6 and 11)]

   The daily pain diary consisted of an 11-point numeric scale ranging from 0 ("no pain") to 10 ("worst possible pain"). Participants described their pain during the past 24 hours by having chosen the appropriate number between 0 and 10. Self-assessment was performed daily each evening before bedtime (6.00 pm to midnight) on the telephone via IVRS. The endpoint mean pain score was defined as the mean of the last 7 daily diary pain ratings while taking study medication in each treatment period - Period 1 and Period 2, respectively. A rating of 1 - 3 was considered as mild pain; 4 - 6 as moderate pain; and 7 - 10 as severe pain.

3. Brief Pain Inventory-Short Form (BPI-sf) Score for Pain-Severity Domain at the End of Each Treatment Period (Week 6 of Each Treatment Period) [End of Period (includes both Visits 6 and 11)]

   The BPI-sf is a self-administered questionnaire developed to assess the severity of pain and the impact of pain on daily functions during a 24 hour period prior to evaluation. The BPI-sf consists of 5 questions: 4 items measure pain (0: no pain; 10: worst pain possible) at its "worst, "least", "average", and "now" (current pain) on an 11-point scale. Scores range from 0 - 40 with higher scores indicating greater pain severity. Another item, containing 7 sub-questions, evaluates the level of interference of pain on daily functioning (general activity, walking, work ability, mood, enjoyment of life, relations with other people, and sleep) on 11-point scales (0: does not interfere; 10: completely interferes). Scores range from 0 - 70 with higher scores indicating greater interference.

4. BPI-sf Score for Pain-Interference Domain at the End of Each Treatment Period (Week 6 of Each Treatment Period) [End of Period (includes both Visits 6 and 11)]

   The BPI-sf is a self-administered questionnaire developed to assess the severity of pain and the impact of pain on daily functions during a 24 hour period prior to evaluation. The BPI-sf consists of 5 questions: 4 items measure pain (0: no pain; 10: worst pain possible) at its "worst, "least", "average", and "now" (current pain) on an 11-point scale. Scores range from 0 - 40 with higher scores indicating greater pain severity. Another item, containing 7 sub-questions, evaluates the level of interference of pain on daily functioning (general activity, walking, work ability, mood, enjoyment of life, relations with other people, and sleep) on 11-point scales (0: does not interfere; 10: completely interferes). Scores range from 0 - 70 with higher scores indicating greater interference.

5. BPI-sf Score for Pain-Interference With Walking Ability at the End of Each Treatment Period (Week 6 of Each Treatment Period) [End of Period (includes both Visits 6 and 11)]

   The BPI-sf is a self-administered questionnaire developed to assess the severity of pain and the impact of pain on daily functions during a 24 hour period prior to evaluation. The BPI-sf consists of 5 questions: 4 items measure pain on an 11-point scale. Scores range from 0 - 40 with higher scores indicating greater pain severity. Another item, containing 7 sub-questions, evaluates the level of interference of pain on daily functioning (general activity, walking, work ability, mood, enjoyment of life, relations with other people, and sleep) on 11-point scales (0: does not interfere; 10: completely interferes). Scores range from 0 - 70 with higher scores indicating greater interference. The sub-score pain interference with walking ability was evaluated, as it was considered to be the most relevant in the context of this study.

6. Daytime Total Activity Counts Per Day Measured by Actigraphy Over the Last 7 Days of Each Treatment Period (Week 6 of Each Treatment Period) [End of Period (includes both Visits 6 and 11)]

   Actigraphy data which measured steps and daytime activity during waking hours were assessed for the last 7 days at Baseline, Visit 6, and Visit 11. Activity counts are the units of motion. It is equal to the sum of peak accelerations each second during the epoch (60 seconds). Total activity counts per day is the sum of the activity counts for each epoch (60 seconds) during the "day" (non-sleep period). Actigraphy was performed with an accelerometer that was worn on the hip during the waking hours. It was programmed to record movements while the device was being worn.

7. Steps Per Day Measured by Actigraphy Over the Last 7 Days of Each Treatment Period (Week 6 of Each Treatment Period) [End of Period (includes both Visits 6 and 11)]

   Actigraphy data which measured steps and daytime activity during waking hours were assessed for the last 7 days at Baseline, Visit 6, and Visit 11. The participants were instructed to wear the device on their hip during the waking hours.

8. Walk 12 Questionnaire Over the Last 2 Weeks of Each Treatment Period (Week 6 of Each Treatment Period) [End of Period (includes both Visits 6 and 11)]

   The Walk-12 is a self-administered questionnaire that assesses the impact of the participant's diabetic neuropathy over the past 2 weeks on parameters associated with walking (12 questions) based on a 5-point scale (from not at all to extremely). The total score is the sum of scores from the 12 questions, which then gets transferred to a 0-100 scale with higher scores indicating greater impairment

9. Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QOL-DN) Total Quality of Life (TQOL) Score Measured Over the Last 2 Weeks of Each Treatment Period (Week 6 of Each Treatment Period) [End of Period (includes both Visits 6 and 11)]

   Norfolk QOL-DN is a 35-item participant-rated questionnaire used to assess impact of diabetic neuropathy on the quality of life of participants with diabetic neuropathy. All symptoms (1 - 7) are scored as either 1 or 0, indicating presence or absence of the symptom. With the exception of questions 31 and 32, the other items are scored according to the 5-point Likert Scale (0 - 4, "no problem" to "severe problem"). In question 31, "good", the middle item, is scored as 0, "very good" as -1, "excellent" as -2, "fair" as 1, and "poor" as 2. In question 32, "about the same", the middle item, is scored as 0, "somewhat better" as -1, "much better" as -2, "somewhat worse" as 1, and "much worse" as 2. TQOL score should be summed as follow: sum (Σ) (1 - 7, 8 - 35). The scales and subscales are calculated without weighting of any kind, and reported as the integer sum of the listed questionnaire items.

10. Norfolk QOL-DN Symptoms Domain Score Measured Over the Last 2 Weeks of Each Treatment Period (Week 6 of Each Treatment Period) [End of Period (includes both Visits 6 and 11)]

    Norfolk QOL-DN is a 35-item participant-rated questionnaire used to assess impact of diabetic neuropathy on the quality of life of participants with diabetic neuropathy. All symptoms (1 - 7) are scored as either 1 or 0, indicating presence or absence of the symptom. With the exception of questions 31 and 32, the other items are scored according to the 5-point Likert Scale (0 - 4, "no problem" to "severe problem"). In question 31, "good", the middle item, is scored as 0, "very good" as -1, "excellent" as -2, "fair" as 1, and "poor" as 2. In question 32, "about the same", the middle item, is scored as 0, "somewhat better" as -1, "much better" as -2, "somewhat worse" as 1, and "much worse" as 2. The symptoms domain score should be summed as follow: Σ(1 - 7, 9). The scales and subscales are calculated without weighting of any kind, and reported as the integer sum of the listed questionnaire items.

11. Norfolk QOL-DN Activities of Daily Living Domain Score Measured Over the Last 2 Weeks of Each Treatment Period (Week 6 of Each Treatment Period) [End of Period (includes both Visits 6 and 11)]

    Norfolk QOL-DN is a 35-item participant-rated questionnaire used to assess impact of diabetic neuropathy on the quality of life of participants with diabetic neuropathy. All symptoms (1 - 7) are scored as either 1 or 0, indicating presence or absence of the symptom. With the exception of questions 31 and 32, the other items are scored according to the 5-point Likert Scale (0 - 4, "no problem" to "severe problem"). In question 31, "good", the middle item, is scored as 0, "very good" as -1, "excellent" as -2, "fair" as 1, and "poor" as 2. In question 32, "about the same", the middle item, is scored as 0, "somewhat better" as -1, "much better" as -2, "somewhat worse" as 1, and "much worse" as 2. The activities of daily living domain score should be summed as follow: Σ(12, 22, 23, 25, 26). The scales and subscales are calculated without weighting of any kind, and reported as the integer sum of the listed questionnaire items.

12. Norfolk QOL-DN Physical Functioning / Large Fiber Domain Score Measured Over the Last 2 Weeks of Each Treatment Period (Week 6 of Each Treatment Period) [End of Period (includes both Visits 6 and 11)]

    Norfolk QOL-DN is a 35-item participant-rated questionnaire used to assess impact of diabetic neuropathy on the quality of life of participants with diabetic neuropathy. All symptoms (1 - 7) are scored as either 1 or 0, indicating presence or absence of the symptom. With the exception of questions 31 and 32, the other items are scored according to the 5-point Likert Scale (0 - 4, "no problem" to "severe problem"). In question 31, "good", the middle item, is scored as 0, "very good" as -1, "excellent" as -2, "fair" as 1, and "poor" as 2. In question 32, "about the same", the middle item, is scored as 0, "somewhat better" as -1, "much better" as -2, "somewhat worse" as 1, and "much worse" as 2. The physical functioning / large fiber domain score should be summed as follow: Σ(8, 11, 13 - 15, 24, 27 - 35). The scales and subscales are calculated without weighting of any kind, and reported as the integer sum of the listed questionnaire items.

13. Norfolk QOL-DN Small Fiber Domain Score Measured Over the Last 2 Weeks of Each Treatment Period (Week 6 of Each Treatment Period) [End of Period (includes both Visits 6 and 11)]

    Norfolk QOL-DN is a 35-item participant-rated questionnaire used to assess impact of diabetic neuropathy on the quality of life of participants with diabetic neuropathy. All symptoms (1 - 7) are scored as either 1 or 0, indicating presence or absence of the symptom. With the exception of questions 31 and 32, the other items are scored according to the 5-point Likert Scale (0 - 4, "no problem" to "severe problem"). In question 31, "good", the middle item, is scored as 0, "very good" as -1, "excellent" as -2, "fair" as 1, and "poor" as 2. In question 32, "about the same", the middle item, is scored as 0, "somewhat better" as -1, "much better" as -2, "somewhat worse" as 1, and "much worse" as 2. The small fiber domain score should be summed as follow: Σ(10, 16, 17, 18). The scales and subscales are calculated without weighting of any kind, and reported as the integer sum of the listed questionnaire items.

14. Norfolk QOL-DN Autonomic Domain Score Measured Over the Last 2 Weeks of Each Treatment Period (Week 6 of Each Treatment Period) [End of Period (includes both Visits 6 and 11)]

    Norfolk QOL-DN is a 35-item participant-rated questionnaire used to assess impact of diabetic neuropathy on the quality of life of participants with diabetic neuropathy. All symptoms (1 - 7) are scored as either 1 or 0, indicating presence or absence of the symptom. With the exception of questions 31 and 32, the other items are scored according to the 5-point Likert Scale (0 - 4, "no problem" to "severe problem"). In question 31, "good", the middle item, is scored as 0, "very good" as -1, "excellent" as -2, "fair" as 1, and "poor" as 2. In question 32, "about the same", the middle item, is scored as 0, "somewhat better" as -1, "much better" as -2, "somewhat worse" as 1, and "much worse" as 2. The autonomic domain score should be summed as follow: Σ(19, 20, 21). The scales and subscales are calculated without weighting of any kind, and reported as the integer sum of the listed questionnaire items.

15. Percentage of Participants With Patient Global Impression of Change (PGIC) Score From Baseline at the End of Period 1 (Week 6) [End of Period 1 (V6)]

    The PGIC is a participant-rated instrument that measures the participant's assessment of change in his/her overall status on a scale ranging from 1 (very much improved) to 7 (very much worse). Original scores (OS; 7 different scores) and categorized scores (CS; 4 different scores) were provided. Categorized scores were very much improved (consisting of very much improved and much improved); any improvement (consisting of very much improved, much improved, and minimally improved); no change (consisting of no change); and any worsening (consisting of minimally worse, much worse, and very much worse). Due to the crossover design, PGIC was analyzed at the end of period 1 (V6).

16. Mean Sleep Interference Rating Score at the End of Each Treatment Period (Week 6 of Each Treatment Period) [End of Period (includes both Visits 6 and 11)]

    The daily sleep diary consists of an 11-point numeric rating scale with which the participant rates how painful DPN pain has interfered with their sleep during the past 24 hours. Zero indicates "does not interfere with sleep" and 10 indicates "completely interferes (unable to sleep due to pain)". Self-assessment was performed daily in the evening before bedtime on a telephone via IVRS (time window for completion between 6.00 pm to midnight) after completion of the daily pain diary.

17. Hospital Anxiety and Depression Scale - Anxiety (HADS-A) Total Score at the End of Each Treatment Period (Week 6 of Each Treatment Period) [End of Period (includes both Visits 6 and 11)]

    The Hospital Anxiety and Depression Scale (HADS) is a 14-item self-administered questionnaire that consists of 2 scales, one measuring anxiety (HADS-A), and the other measuring depression (HADS-D). Each subscale consists of 7 statements and the participant responds as to how each item applies to him/her over the past week on 4-point response scale. Separate scores are calculated for anxiety and depression and a score (ranging from 0 to 21) is obtained for each subscale. The higher the score, the more severe the anxiety or depression.

18. Hospital Anxiety and Depression Scale - Depression (HADS-D) Total Score at the End of Each Treatment Period (Week 6 of Each Treatment Period) [End of Period (includes both Visits 6 and 11)]

    The HADS is a 14-item self-administered questionnaire that consists of 2 scales, one measuring anxiety (HADS-A), and the other measuring depression (HADS-D). Each subscale consists of 7 statements and the participant responds as to how each item applies to him/her over the past week on 4-point response scale. Separate scores are calculated for anxiety and depression and a score (ranging from 0 to 21) is obtained for each subscale. The higher the score, the more severe the anxiety or depression.

19. Euro QoL-5 Dimensions (EQ-5D) - Health State Profile Utility Scores at the End of Each Treatment Period (Week 6 of Each Treatment Period) [End of Period (includes both Visits 6 and 11)]

    The EQ-5D describes participant's health status based on 5 attributes producing an 5 digit index score. The 5 dimensions are: mobility, self-care, usual activities, pain / discomfort, and anxiety / depression. Dolan 1997 advised how to transfer this index score to a single score for clinical trials, a revised single index was published in 2001. The index uses general population weighted estimates for various health states. In general, the range of the single index tends to vary between 0 = death and 1 = perfect health and there are some states that have been rated by the general population to be worse than death which may result in numbers below 0.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Men or women who are at least 18 years old.

• Diagnosis of painful diabetic peripheral neuropathy.

• Pain on walking.

Exclusion Criteria:

• Inability to walk 50 feet on a flat surface.

• Pain on walking due to conditions other than diabetic peripheral neuropathy.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Dedicated Clinical Research	Goodyear	Arizona	United States	85395
2	Arizona Research Center	Phoenix	Arizona	United States	85023
3	Neuro-Pain Medical Center	Fresno	California	United States	93710
4	HealthCare Partners Medical Group	Los Angeles	California	United States	90015
5	IDS Pharmacy	Los Angeles	California	United States	90033
6	University of Southern California	Los Angeles	California	United States	90033
7	PAB Clinical Research	Brandon	Florida	United States	33511
8	Pulmonary Associates of Brandon	Brandon	Florida	United States	33511
9	Innovative Research of West Florida, Inc.	Clearwater	Florida	United States	33756
10	The Office of Laszlo Jozef Mate, MD	North Palm Beach	Florida	United States	33408
11	Meridien Research	Tampa	Florida	United States	33606
12	Metabolic Research Institute, Inc.	West Palm Beach	Florida	United States	33401
13	Clinical Research of Central Florida	Winter Haven	Florida	United States	33880
14	Columbus Research Foundation	Columbus	Georgia	United States	31904
15	MediSphere Medical Research Center, LLC	Evansville	Indiana	United States	47714
16	Heartland Research Associates, LLC	Wichita	Kansas	United States	67205
17	Quality Clinical Research, Inc.	Omaha	Nebraska	United States	68114
18	Desert Endocrinology Clinical Research Center	Henderson	Nevada	United States	89052
19	Clinical Research Consortium	Las Vegas	Nevada	United States	89119
20	The Office of Dr. Stephen H. Miller, MD	Las Vegas	Nevada	United States	89144
21	The Medical Research Network, LLC	New York	New York	United States	10128
22	Neurology and Neuroscience Center of Ohio	Toledo	Ohio	United States	43623
23	Sooner Clinical Research	Oklahoma City	Oklahoma	United States	73112
24	The Office of Veronique Sebastian, MD	Oklahoma City	Oklahoma	United States	73120
25	Sunstone Medical Research, LLC	Medford	Oregon	United States	97504
26	Oregon Health and Science University - Comprehensive Pain Center	Portland	Oregon	United States	97239
27	Oregon Health and Science University - Department of Anesthesiology and Perioperative Medicine	Portland	Oregon	United States	97239
28	Blair Orthopedic Associates, Inc.	Altoona	Pennsylvania	United States	16602
29	Altoona Center for Clinical Research	Duncansville	Pennsylvania	United States	16635
30	Memorial Hospital of Rhode Island	Pawtucket	Rhode Island	United States	02860
31	Neurology and Pain Clinic, LLC	Orangeburg	South Carolina	United States	29118
32	Houston Neurocare	Houston	Texas	United States	77030
33	Centex Research, Inc.	Houston	Texas	United States	77062
34	Eastern Virginia Medical School	Norfolk	Virginia	United States	23507
35	Privatni specializovana ambulance pro neurologii a detskou neurologii	Brno-Bystrc		Czechia	635 00
36	Clintrial, s.r.o.	Praha 10		Czechia	100 00
37	Fakultni nemocnice v Motole	Praha 5		Czechia	150 06
38	Dr DR Lakha's Practice	Johannesburg	Gauteng	South Africa	1829
39	Dr Hemant Makan (Private Practice)	Lenasia	Gauteng	South Africa	1820
40	Randles Road Medical Centre	Durban	Kwa-Zulu Natal	South Africa	4000
41	Richards Bay Trial Centre	Richards Bay		South Africa	3900
42	Forskningsmottagningen Gamla Sjukhuset i Falkoping	Falkoping		Sweden	521 43
43	Center for Lakemedelsstudier	Malmo		Sweden	211 52
44	Citydiabetes	Stockholm		Sweden	111 57
45	Bragee Medect AB	Stockholm		Sweden	115 22

Sponsors and Collaborators

• Pfizer's Upjohn has merged with Mylan to form Viatris Inc.

Investigators

• Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• To obtain contact information for a study center near you, click here.

Publications

None provided.

• Responsible Party: Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
• ClinicalTrials.gov Identifier: NCT01474772
• Other Study ID Numbers: A0081269; 2011-003266-32
• First Posted: Nov 18, 2011
• Last Update Posted: Jan 28, 2021
• Last Verified: Nov 1, 2014

• Keywords provided by Pfizer's Upjohn has merged with Mylan to form Viatris Inc.: Diabetic Peripheral Neuropathy; Pain on Walking; Pregabalin
• Additional relevant MeSH terms: Peripheral Nervous System Diseases; Diabetic Neuropathies; Pregabalin

Study Results

Participant Flow

Recruitment Details	411 participants were screened, of whom 206 were withdrawn before randomization. 205 were randomized, of whom 2 discontinued before being treated. Participants were randomized at 36 centers in 4 countries: US (25), Sweden (4), South Africa (4), and Czech Republic (3). 11 centers received study drug but did not randomize participants.
Pre-assignment Detail	Participants completed daily pain and sleep diary from Visit 1 (V1; Screening) to Visit 12 (V12; Follow-up). Participants with a mean pain score ≥ 4 (moderate to severe pain) and those meeting the pain on walking criteria (post-walk pain score ≥ 4, and > the pre-walk pain score at V1 and Visit 2 [V2; Baseline]) were randomized.

Arm/Group Title	Pregabalin/Placebo	Placebo/Pregablin
Arm/Group Description	Participants were randomized to double-blind treatment with pregabalin for 6 weeks (2 week dose titration [starting dose: 150 mg/day] and 4 weeks fixed dose [150 - 300 mg/day]) in period 1 followed by placebo in period 2. There was a 2-week single-blind washout (blinded to participant) between the treatment periods. A 1-week taper was administered at the end of the second treatment period, followed by a final follow-up visit.	Participants were randomized to double-blind treatment with placebo for 6 weeks in period 1 followed by pregabalin in period 2 (2 week dose titration [starting dose: 150 mg/day] and 4 weeks fixed dose [150 - 300 mg/day]). There was a 2-week single-blind washout (blinded to participant) between the treatment periods. A 1-week taper was administered at the end of the second treatment period, followed by a final follow-up visit.
Period Title: Period 1
STARTED	101	102
COMPLETED	89	99
NOT COMPLETED	12	3
Period Title: Period 1
STARTED	89	99
COMPLETED	86	97
NOT COMPLETED	3	2
Period Title: Period 1
STARTED	86	97
COMPLETED	77	87
NOT COMPLETED	9	10
Period Title: Period 1
STARTED	77	87
COMPLETED	77	86
NOT COMPLETED	0	1

Baseline Characteristics

Arm/Group Title	Pregabalin/Placebo	Placebo/Pregabalin	Total
Arm/Group Description	Participants were randomized to double-blind treatment with pregabalin for 6 weeks (2 week dose titration [starting dose: 150 mg/day] and 4 weeks fixed dose [150 - 300 mg/day]) in period 1 followed by placebo in period 2. There was a 2-week single-blind washout (blinded to participant) between the treatment periods. A 1-week taper was administered at the end of the second treatment period, followed by a final follow-up visit.	Participants were randomized to double-blind treatment with placebo for 6 weeks in period 1 followed by pregabalin in period 2 (2 week dose titration [starting dose: 150 mg/day] and 4 weeks fixed dose [150 - 300 mg/day]). There was a 2-week single-blind washout (blinded to participant) between the treatment periods. A 1-week taper was administered at the end of the second treatment period, followed by a final follow-up visit.	Total of all reporting groups
Overall Participants	101	102	203
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	59.1 (8.5)	58.4 (9.3)	58.7 (8.9)
Sex: Female, Male (Count of Participants)
Female	40 39.6%	31 30.4%	71 35%
Male	61 60.4%	71 69.6%	132 65%

Outcome Measures

1. Primary Outcome

Title	Average Diabetic Peripheral Neuropathy (DPN) Pain Based on a Numeric Rating Scale (NRS) Over the Last 7 Days of Each Treatment Period (Week 6 of Each Treatment Period)
Description	The daily pain diary consisted of an 11-point numeric scale ranging from 0 ("no pain") to 10 ("worst possible pain"). Participants described their pain during the past 24 hours by having chosen the appropriate number between 0 and 10. Self-assessment was performed daily each evening before bedtime (6.00 pm to midnight) on the telephone via Interactive Voice Recognition System (IVRS). The endpoint mean pain score was defined as the mean of the last 7 daily diary pain ratings while taking study medication in each treatment period - Period 1 and Period 2, respectively. A rating of 1 - 3 was considered as mild pain; 4 - 6 as moderate pain; and 7 - 10 as severe pain.
Time Frame	End of Period (includes both Visits 6 and 11)

Outcome Measure Data

Analysis Population Description

All participants who were randomized, treated (ie, received at least one dose of study medication) and had at least one post-randomization efficacy evaluation were included in the Intent-to-Treat (ITT) analysis (N: 203). This was the primary analysis set.

Arm/Group Title	Pregabalin	Placebo
Arm/Group Description	The below table included data from participants while receiving pregabalin in either period of the 2-period crossover study design. This crossover study consisted of two double blind 6-week treatment periods where participants were randomized to pregabalin or placebo for the first period, and were then switched to the other treatment for the second period (2 weeks dose titration and 4 weeks fixed dose for each treatment period). There was a 2-week single-blind washout (blinded to participant) between the treatment periods. A 1-week taper was administered at the end of the second treatment period, followed by a final follow-up visit.	The below table included data from participants while receiving placebo in either period of the 2-period crossover study design. This crossover study consisted of two double blind 6-week treatment periods where participants were randomized to pregabalin or placebo for the first period, and were then switched to the other treatment for the second period (2 weeks dose titration and 4 weeks fixed dose for each treatment period). There was a 2-week single-blind washout (blinded to participant) between the treatment periods. A 1-week taper was administered at the end of the second treatment period, followed by a final follow-up visit.
Measure Participants	198	186
Least Squares Mean (Standard Error) [units on a scale]	4.73 (0.14)	4.96 (0.14)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments	Analysis was done using a linear mixed effects model including baseline pain, sequence, period, center, and treatment as fixed effect factors and participant within sequence and within-participant error as random factors. Last observation carried forward (LOCF) approach was applied.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0659
	Comments	Primary analysis was two-sided and performed at the 0.05 significance level. The study was considered positive only if both co-primary endpoints had p-values that were less than 0.05, hence there was no need for multiplicity adjustment.
	Method	Linear mixed effects model
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.22
	Confidence Interval	(2-Sided) 95%; -0.46 to 0.01
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.12
	Estimation Comments

2. Post-Hoc Outcome

Title	Average Weekly DPN Pain Based on a NRS (Baseline, 6 Weeks in Period 1, 2 Weeks Washout and 6 Weeks in Period 2)
Description	The daily pain diary consisted of an 11-point numeric scale ranging from 0 ("no pain") to 10 ("worst possible pain"). Participants described their pain during the past 24 hours by having chosen the appropriate number between 0 and 10. Self-assessment was performed daily each evening before bedtime (6.00 pm to midnight) on the telephone via IVRS. The longitudinal mean weekly DPN pain scores were defined as the mean of 7 daily diary pain ratings. A rating of 1 - 3 was considered as mild pain; 4 - 6 as moderate pain; and 7 - 10 as severe pain.
Time Frame	Baseline, 6 weeks in Period 1, 2 weeks washout and 6 weeks in Period 2

Outcome Measure Data

Analysis Population Description

All participants who were randomized, treated (ie, received at least one dose of study medication) and had at least one post-randomization efficacy evaluation were included in the ITT analysis (N: 203). Numbers of participants analyzed are provided in section Measured Values in brackets (N: Pregabalin, Placebo).

Arm/Group Title	Pregabalin	Placebo
Arm/Group Description	The below table included data from participants while receiving pregabalin in either period of the 2-period crossover study design. This crossover study consisted of two double blind 6-week treatment periods where participants were randomized to pregabalin or placebo for the first period, and were then switched to the other treatment for the second period (2 weeks dose titration and 4 weeks fixed dose for each treatment period). There was a 2-week single-blind washout (blinded to participant) between the treatment periods. A 1-week taper was administered at the end of the second treatment period, followed by a final follow-up visit.	The below table included data from participants while receiving placebo in either period of the 2-period crossover study design. This crossover study consisted of two double blind 6-week treatment periods where participants were randomized to pregabalin or placebo for the first period, and were then switched to the other treatment for the second period (2 weeks dose titration and 4 weeks fixed dose for each treatment period). There was a 2-week single-blind washout (blinded to participant) between the treatment periods. A 1-week taper was administered at the end of the second treatment period, followed by a final follow-up visit.
Measure Participants	198	186
V6 (N: 101, 102)	4.66 (1.77)	5.29 (1.93)
V11 (N: 97, 84)	4.57 (2.22)	4.38 (2.17)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments	This longitudinal analysis was a sensitivity analysis of the primary endpoint. P-value was based on a repeated measure mixed effects model including pooled center, time point, treatment, an indicator variable for Week 6 as well as interaction terms as fixed effect factors. For analysis purpose, it is assumed that participants were on placebo at Baseline, took the same treatment as in Period 1 during Week 1 of washout, and were on placebo in Week 2 of washout.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0242
	Comments	Primary analysis was two-sided and performed at the 0.05 significance level. Unstructured covariance structure was used to estimate the within-participant errors.
	Method	Repeated measure mixed effects model
	Comments	The Kenward-Roger method was used to estimate denominator degrees of freedom.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.291
	Confidence Interval	(2-Sided) 95%; -0.543 to -0.038
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.128
	Estimation Comments

3. Primary Outcome

Title	DPN Pain on Walking Based on a 11-point NRS of Each Treatment Period (Week 6 of Each Treatment Period)
Description	The post-test DPN pain on walking NRS consisted of an 11-point numeric scale ranging from 0 ("no pain") to 10 ("worst possible pain"). Participants described their DPN pain in their legs and/or feet while walking during the 50-foot walk test by choosing the appropriate number between 0 and 10. The post-test DPN pain on walking NRS was completed by the participant using paper-pen administration immediately after completing the 50-foot walk test at the end of each treatment period - Period 1 and Period 2, respectively. A rating of 1 - 3 was considered as mild pain; 4 - 6 as moderate pain; and 7 - 10 as severe pain.
Time Frame	End of Period (includes both Visits 6 and 11)

Outcome Measure Data

Analysis Population Description

All participants who were randomized, treated (ie, received at least one dose of study medication) and had at least one post-randomization efficacy evaluation were included in the ITT analysis (N: 203). This was the primary analysis set.

Arm/Group Title	Pregabalin	Placebo
Arm/Group Description	The below table included data from participants while receiving pregabalin in either period of the 2-period crossover study design. This crossover study consisted of two double blind 6-week treatment periods where participants were randomized to pregabalin or placebo for the first period, and were then switched to the other treatment for the second period (2 weeks dose titration and 4 weeks fixed dose for each treatment period). There was a 2-week single-blind washout (blinded to participant) between the treatment periods. A 1-week taper was administered at the end of the second treatment period, followed by a final follow-up visit.	The below table included data from participants while receiving placebo in either period of the 2-period crossover study design. This crossover study consisted of two double blind 6-week treatment periods where participants were randomized to pregabalin or placebo for the first period, and were then switched to the other treatment for the second period (2 weeks dose titration and 4 weeks fixed dose for each treatment period). There was a 2-week single-blind washout (blinded to participant) between the treatment periods. A 1-week taper was administered at the end of the second treatment period, followed by a final follow-up visit.
Measure Participants	198	186
Least Squares Mean (Standard Error) [units on a scale]	4.28 (0.15)	4.41 (0.15)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments	Analysis was done using a repeated measure linear mixed effects model including baseline pain, sequence, period, center, time, treatment, and treatment by time interaction as fixed effect factors and participant within sequence and within-participant error as random factors. The model term 'time' may take 2 values corresponding to Week 3 and Week 6 in each period.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.4120
	Comments	Primary analysis was two-sided and performed at the 0.05 significance level. The study was considered positive only if both co-primary endpoints have p-values that are less than 0.05, hence there was no need for multiplicity adjustment.
	Method	Mixed-Effect Model Repeated Measures
	Comments	Satterthwaite's approximation was used to estimate denominator degrees of freedom.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.13
	Confidence Interval	(2-Sided) 95%; -0.44 to 0.18
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.16
	Estimation Comments

4. Secondary Outcome

Title	Percentage of Participants Achieving 30% Reduction in Mean DPN Pain Score From Baseline at the End of Each Treatment Period (Week 6 of Each Treatment Period)
Description	The daily pain diary consisted of an 11-point numeric scale ranging from 0 ("no pain") to 10 ("worst possible pain"). Participants described their pain during the past 24 hours by having chosen the appropriate number between 0 and 10. Self-assessment was performed daily each evening before bedtime (6.00 pm to midnight) on the telephone via IVRS. The endpoint mean pain score was defined as the mean of the last 7 daily diary pain ratings while taking study medication in each treatment period - Period 1 and Period 2, respectively. A rating of 1 - 3 was considered as mild pain; 4 - 6 as moderate pain; and 7 - 10 as severe pain.
Time Frame	End of Period (includes both Visits 6 and 11)

Outcome Measure Data

Analysis Population Description

All participants who were randomized, treated (ie, received at least one dose of study medication) and had at least one post-randomization efficacy evaluation were included in the ITT analysis (N: 203). This was the primary analysis set. Numbers of participants analyzed are provided in section Measured Values in brackets (N: Pregabalin, Placebo).

Arm/Group Title	Pregabalin	Placebo
Arm/Group Description	The below table included data from participants while receiving pregabalin in either period of the 2-period crossover study design. This crossover study consisted of two double blind 6-week treatment periods where participants were randomized to pregabalin or placebo for the first period, and were then switched to the other treatment for the second period (2 weeks dose titration and 4 weeks fixed dose for each treatment period). There was a 2-week single-blind washout (blinded to participant) between the treatment periods. A 1-week taper was administered at the end of the second treatment period, followed by a final follow-up visit.	The below table included data from participants while receiving placebo in either period of the 2-period crossover study design. This crossover study consisted of two double blind 6-week treatment periods where participants were randomized to pregabalin or placebo for the first period, and were then switched to the other treatment for the second period (2 weeks dose titration and 4 weeks fixed dose for each treatment period). There was a 2-week single-blind washout (blinded to participant) between the treatment periods. A 1-week taper was administered at the end of the second treatment period, followed by a final follow-up visit.
Measure Participants	198	186
V6 (N: 101, 102)	38.6 38.2%	24.5 24%
V11 (N: 97, 84)	46.4 45.9%	47.6 46.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments	Analysis was done overall (period 1 and period 2) using a generalized linear mixed model which included response as the dependent variable, sequence, period, pooled center, treatment as fixed effects, and subject within treatment as random effect. LOCF approach was applied.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0847
	Comments	Secondary analysis was two-sided and performed at the 0.05 significance level. No corrections to alpha to control for potential inflation of Type I error resulting from multiple comparisons were made.
	Method	Generalized linear mixed model
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.55
	Confidence Interval	(2-Sided) 95%; 0.94 to 2.55
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Percentage of Participants Achieving 50% Reduction in Mean DPN Pain Score From Baseline at the End of Each Treatment Period (Week 6 of Each Treatment Period)
Description	The daily pain diary consisted of an 11-point numeric scale ranging from 0 ("no pain") to 10 ("worst possible pain"). Participants described their pain during the past 24 hours by having chosen the appropriate number between 0 and 10. Self-assessment was performed daily each evening before bedtime (6.00 pm to midnight) on the telephone via IVRS. The endpoint mean pain score was defined as the mean of the last 7 daily diary pain ratings while taking study medication in each treatment period - Period 1 and Period 2, respectively. A rating of 1 - 3 was considered as mild pain; 4 - 6 as moderate pain; and 7 - 10 as severe pain.
Time Frame	End of Period (includes both Visits 6 and 11)

Outcome Measure Data

Analysis Population Description

All participants who were randomized, treated (ie, received at least one dose of study medication) and had at least one post-randomization efficacy evaluation were included in the ITT analysis (N: 203). This was the primary analysis set. Numbers of participants analyzed are provided in section Measured Values in brackets (N: Pregabalin, Placebo).

Arm/Group Title	Pregabalin	Placebo
Arm/Group Description	The below table included data from participants while receiving pregabalin in either period of the 2-period crossover study design. This crossover study consisted of two double blind 6-week treatment periods where participants were randomized to pregabalin or placebo for the first period, and were then switched to the other treatment for the second period (2 weeks dose titration and 4 weeks fixed dose for each treatment period). There was a 2-week single-blind washout (blinded to participant) between the treatment periods. A 1-week taper was administered at the end of the second treatment period, followed by a final follow-up visit.	The below table included data from participants while receiving placebo in either period of the 2-period crossover study design. This crossover study consisted of two double blind 6-week treatment periods where participants were randomized to pregabalin or placebo for the first period, and were then switched to the other treatment for the second period (2 weeks dose titration and 4 weeks fixed dose for each treatment period). There was a 2-week single-blind washout (blinded to participant) between the treatment periods. A 1-week taper was administered at the end of the second treatment period, followed by a final follow-up visit.
Measure Participants	198	186
V6 (N: 101, 102)	23.8 23.6%	13.7 13.4%
V11 (N: 97, 84)	27.8 27.5%	32.1 31.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments	Analysis was done overall (period 1 and period 2) using a generalized linear mixed model which included response as the dependent variable, sequence, period, pooled center, treatment as fixed effects, and subject within treatment as random effect. LOCF approach was applied.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.2459
	Comments	Secondary analysis was two-sided and performed at the 0.05 significance level. No corrections to alpha to control for potential inflation of Type I error resulting from multiple comparisons were made.
	Method	Generalized linear mixed model
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.38
	Confidence Interval	(2-Sided) 95%; 0.80 to 2.39
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Brief Pain Inventory-Short Form (BPI-sf) Score for Pain-Severity Domain at the End of Each Treatment Period (Week 6 of Each Treatment Period)
Description	The BPI-sf is a self-administered questionnaire developed to assess the severity of pain and the impact of pain on daily functions during a 24 hour period prior to evaluation. The BPI-sf consists of 5 questions: 4 items measure pain (0: no pain; 10: worst pain possible) at its "worst, "least", "average", and "now" (current pain) on an 11-point scale. Scores range from 0 - 40 with higher scores indicating greater pain severity. Another item, containing 7 sub-questions, evaluates the level of interference of pain on daily functioning (general activity, walking, work ability, mood, enjoyment of life, relations with other people, and sleep) on 11-point scales (0: does not interfere; 10: completely interferes). Scores range from 0 - 70 with higher scores indicating greater interference.
Time Frame	End of Period (includes both Visits 6 and 11)

Outcome Measure Data

Analysis Population Description

All participants who were randomized, treated (ie, received at least one dose of study medication) and had at least one post-randomization efficacy evaluation were included in the ITT analysis (N: 203). This was the primary analysis set.

Arm/Group Title	Pregabalin	Placebo
Arm/Group Description	The below table included data from participants while receiving pregabalin in either period of the 2-period crossover study design. This crossover study consisted of two double blind 6-week treatment periods where participants were randomized to pregabalin or placebo for the first period, and were then switched to the other treatment for the second period (2 weeks dose titration and 4 weeks fixed dose for each treatment period). There was a 2-week single-blind washout (blinded to participant) between the treatment periods. A 1-week taper was administered at the end of the second treatment period, followed by a final follow-up visit.	The below table included data from participants while receiving placebo in either period of the 2-period crossover study design. This crossover study consisted of two double blind 6-week treatment periods where participants were randomized to pregabalin or placebo for the first period, and were then switched to the other treatment for the second period (2 weeks dose titration and 4 weeks fixed dose for each treatment period). There was a 2-week single-blind washout (blinded to participant) between the treatment periods. A 1-week taper was administered at the end of the second treatment period, followed by a final follow-up visit.
Measure Participants	198	186
Least Squares Mean (Standard Error) [units on a scale]	16.76 (0.56)	17.56 (0.75)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments	Analysis was done using a linear mixed effects model including baseline pain, sequence, period, center, and treatment as fixed effect factors and participant within sequence and within-participant error as random factors.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0889
	Comments	Secondary analysis was two-sided and performed at the 0.05 significance level. No corrections to alpha to control for potential inflation of Type I error resulting from multiple comparisons were made.
	Method	Linear mixed effects model
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.80
	Confidence Interval	(2-Sided) 95%; -1.71 to 0.12
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.46
	Estimation Comments

7. Secondary Outcome

Title	BPI-sf Score for Pain-Interference Domain at the End of Each Treatment Period (Week 6 of Each Treatment Period)
Description	The BPI-sf is a self-administered questionnaire developed to assess the severity of pain and the impact of pain on daily functions during a 24 hour period prior to evaluation. The BPI-sf consists of 5 questions: 4 items measure pain (0: no pain; 10: worst pain possible) at its "worst, "least", "average", and "now" (current pain) on an 11-point scale. Scores range from 0 - 40 with higher scores indicating greater pain severity. Another item, containing 7 sub-questions, evaluates the level of interference of pain on daily functioning (general activity, walking, work ability, mood, enjoyment of life, relations with other people, and sleep) on 11-point scales (0: does not interfere; 10: completely interferes). Scores range from 0 - 70 with higher scores indicating greater interference.
Time Frame	End of Period (includes both Visits 6 and 11)

Outcome Measure Data

Analysis Population Description

All participants who were randomized, treated (ie, received at least one dose of study medication) and had at least one post-randomization efficacy evaluation were included in the ITT analysis (N: 203). This was the primary analysis set.

Arm/Group Title	Pregabalin	Placebo
Arm/Group Description	The below table included data from participants while receiving pregabalin in either period of the 2-period crossover study design. This crossover study consisted of two double blind 6-week treatment periods where participants were randomized to pregabalin or placebo for the first period, and were then switched to the other treatment for the second period (2 weeks dose titration and 4 weeks fixed dose for each treatment period). There was a 2-week single-blind washout (blinded to participant) between the treatment periods. A 1-week taper was administered at the end of the second treatment period, followed by a final follow-up visit.	The below table included data from participants while receiving placebo in either period of the 2-period crossover study design. This crossover study consisted of two double blind 6-week treatment periods where participants were randomized to pregabalin or placebo for the first period, and were then switched to the other treatment for the second period (2 weeks dose titration and 4 weeks fixed dose for each treatment period). There was a 2-week single-blind washout (blinded to participant) between the treatment periods. A 1-week taper was administered at the end of the second treatment period, followed by a final follow-up visit.
Measure Participants	198	186
Least Squares Mean (Standard Error) [units on a scale]	22.58 (0.96)	23.75 (0.98)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments	Analysis was done using a linear mixed effects model including baseline pain, sequence, period, center, and treatment as fixed effect factors and participant within sequence and within-participant error as random factors.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.1781
	Comments	Secondary analysis was two-sided and performed at the 0.05 significance level. No corrections to alpha to control for potential inflation of Type I error resulting from multiple comparisons were made.
	Method	Linear mixed effects model
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.16
	Confidence Interval	(2-Sided) 95%; -2.86 to 0.53
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.86
	Estimation Comments

8. Secondary Outcome

Title	BPI-sf Score for Pain-Interference With Walking Ability at the End of Each Treatment Period (Week 6 of Each Treatment Period)
Description	The BPI-sf is a self-administered questionnaire developed to assess the severity of pain and the impact of pain on daily functions during a 24 hour period prior to evaluation. The BPI-sf consists of 5 questions: 4 items measure pain on an 11-point scale. Scores range from 0 - 40 with higher scores indicating greater pain severity. Another item, containing 7 sub-questions, evaluates the level of interference of pain on daily functioning (general activity, walking, work ability, mood, enjoyment of life, relations with other people, and sleep) on 11-point scales (0: does not interfere; 10: completely interferes). Scores range from 0 - 70 with higher scores indicating greater interference. The sub-score pain interference with walking ability was evaluated, as it was considered to be the most relevant in the context of this study.
Time Frame	End of Period (includes both Visits 6 and 11)

Outcome Measure Data

Analysis Population Description

All participants who were randomized, treated (ie, received at least one dose of study medication) and had at least one post-randomization efficacy evaluation were included in the ITT analysis (N: 203). This was the primary analysis set.

Arm/Group Title	Pregabalin	Placebo
Arm/Group Description	The below table included data from participants while receiving pregabalin in either period of the 2-period crossover study design. This crossover study consisted of two double blind 6-week treatment periods where participants were randomized to pregabalin or placebo for the first period, and were then switched to the other treatment for the second period (2 weeks dose titration and 4 weeks fixed dose for each treatment period). There was a 2-week single-blind washout (blinded to participant) between the treatment periods. A 1-week taper was administered at the end of the second treatment period, followed by a final follow-up visit.	The below table included data from participants while receiving placebo in either period of the 2-period crossover study design. This crossover study consisted of two double blind 6-week treatment periods where participants were randomized to pregabalin or placebo for the first period, and were then switched to the other treatment for the second period (2 weeks dose titration and 4 weeks fixed dose for each treatment period). There was a 2-week single-blind washout (blinded to participant) between the treatment periods. A 1-week taper was administered at the end of the second treatment period, followed by a final follow-up visit.
Measure Participants	198	186
Least Squares Mean (Standard Error) [units on a scale]	3.75 (0.17)	3.93 (0.18)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments	Analysis was done using a linear mixed effects model including baseline pain, sequence, period, center, and treatment as fixed effect factors and participant within sequence and within-participant error as random factors.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.2719
	Comments	Secondary analysis was two-sided and performed at the 0.05 significance level. No corrections to alpha to control for potential inflation of Type I error resulting from multiple comparisons were made.
	Method	Linear mixed effects model
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.19
	Confidence Interval	(2-Sided) 95%; -0.53 to 0.15
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.17
	Estimation Comments

9. Secondary Outcome

Title	Daytime Total Activity Counts Per Day Measured by Actigraphy Over the Last 7 Days of Each Treatment Period (Week 6 of Each Treatment Period)
Description	Actigraphy data which measured steps and daytime activity during waking hours were assessed for the last 7 days at Baseline, Visit 6, and Visit 11. Activity counts are the units of motion. It is equal to the sum of peak accelerations each second during the epoch (60 seconds). Total activity counts per day is the sum of the activity counts for each epoch (60 seconds) during the "day" (non-sleep period). Actigraphy was performed with an accelerometer that was worn on the hip during the waking hours. It was programmed to record movements while the device was being worn.
Time Frame	End of Period (includes both Visits 6 and 11)

Outcome Measure Data

Analysis Population Description

All participants who were randomized, treated (ie, received at least one dose of study medication) and had at least one post-randomization efficacy evaluation were included in the ITT analysis (N: 203). This was the primary analysis set.

Arm/Group Title	Pregabalin	Placebo
Arm/Group Description	The below table included data from participants while receiving pregabalin in either period of the 2-period crossover study design. This crossover study consisted of two double blind 6-week treatment periods where participants were randomized to pregabalin or placebo for the first period, and were then switched to the other treatment for the second period (2 weeks dose titration and 4 weeks fixed dose for each treatment period). There was a 2-week single-blind washout (blinded to participant) between the treatment periods. A 1-week taper was administered at the end of the second treatment period, followed by a final follow-up visit.	The below table included data from participants while receiving placebo in either period of the 2-period crossover study design. This crossover study consisted of two double blind 6-week treatment periods where participants were randomized to pregabalin or placebo for the first period, and were then switched to the other treatment for the second period (2 weeks dose titration and 4 weeks fixed dose for each treatment period). There was a 2-week single-blind washout (blinded to participant) between the treatment periods. A 1-week taper was administered at the end of the second treatment period, followed by a final follow-up visit.
Measure Participants	198	186
Least Squares Mean (Standard Error) [counts]	64703.14 (4005.00)	64139.75 (4057.89)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments	Analysis was done using a linear mixed effects model including baseline value, sequence, period, center, and treatment as fixed effect factors and participant within sequence and within-participant error as random factors. LOCF approach was applied.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.8909
	Comments	Secondary analysis was two-sided and performed at the 0.05 significance level. No corrections to alpha to control for potential inflation of Type I error resulting from multiple comparisons were made.
	Method	Linear mixed effects model
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	563.39
	Confidence Interval	(2-Sided) 95%; -7549.82 to 8676.60
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 4098.74
	Estimation Comments

10. Secondary Outcome

Title	Steps Per Day Measured by Actigraphy Over the Last 7 Days of Each Treatment Period (Week 6 of Each Treatment Period)
Description	Actigraphy data which measured steps and daytime activity during waking hours were assessed for the last 7 days at Baseline, Visit 6, and Visit 11. The participants were instructed to wear the device on their hip during the waking hours.
Time Frame	End of Period (includes both Visits 6 and 11)

Outcome Measure Data

Analysis Population Description

All participants who were randomized, treated (ie, received at least one dose of study medication) and had at least one post-randomization efficacy evaluation were included in the ITT analysis (N: 203). This was the primary analysis set.

Arm/Group Title	Pregabalin	Placebo
Arm/Group Description	The below table included data from participants while receiving pregabalin in either period of the 2-period crossover study design. This crossover study consisted of two double blind 6-week treatment periods where participants were randomized to pregabalin or placebo for the first period, and were then switched to the other treatment for the second period (2 weeks dose titration and 4 weeks fixed dose for each treatment period). There was a 2-week single-blind washout (blinded to participant) between the treatment periods. A 1-week taper was administered at the end of the second treatment period, followed by a final follow-up visit.	The below table included data from participants while receiving placebo in either period of the 2-period crossover study design. This crossover study consisted of two double blind 6-week treatment periods where participants were randomized to pregabalin or placebo for the first period, and were then switched to the other treatment for the second period (2 weeks dose titration and 4 weeks fixed dose for each treatment period). There was a 2-week single-blind washout (blinded to participant) between the treatment periods. A 1-week taper was administered at the end of the second treatment period, followed by a final follow-up visit.
Measure Participants	198	186
Least Squares Mean (Standard Error) [steps]	3785.65 (201.17)	3788.28 (203.05)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments	Analysis was done using a linear mixed effects model including baseline value, sequence, period, center, and treatment as fixed effect factors and participant within sequence and within-participant error as random factors. LOCF approach was applied.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.9899
	Comments	Secondary analysis was two-sided and performed at the 0.05 significance level. No corrections to alpha to control for potential inflation of Type I error resulting from multiple comparisons were made.
	Method	Linear mixed effects model
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.63
	Confidence Interval	(2-Sided) 95%; -411.26 to 406.01
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 206.37
	Estimation Comments

11. Secondary Outcome

Title	Walk 12 Questionnaire Over the Last 2 Weeks of Each Treatment Period (Week 6 of Each Treatment Period)
Description	The Walk-12 is a self-administered questionnaire that assesses the impact of the participant's diabetic neuropathy over the past 2 weeks on parameters associated with walking (12 questions) based on a 5-point scale (from not at all to extremely). The total score is the sum of scores from the 12 questions, which then gets transferred to a 0-100 scale with higher scores indicating greater impairment
Time Frame	End of Period (includes both Visits 6 and 11)

Outcome Measure Data

Analysis Population Description

All participants who were randomized, treated (ie, received at least one dose of study medication) and had at least one post-randomization efficacy evaluation were included in the ITT analysis (N: 203). This was the primary analysis set.

Arm/Group Title	Pregabalin	Placebo
Arm/Group Description	The below table included data from participants while receiving pregabalin in either period of the 2-period crossover study design. This crossover study consisted of two double blind 6-week treatment periods where participants were randomized to pregabalin or placebo for the first period, and were then switched to the other treatment for the second period (2 weeks dose titration and 4 weeks fixed dose for each treatment period). There was a 2-week single-blind washout (blinded to participant) between the treatment periods. A 1-week taper was administered at the end of the second treatment period, followed by a final follow-up visit.	The below table included data from participants while receiving placebo in either period of the 2-period crossover study design. This crossover study consisted of two double blind 6-week treatment periods where participants were randomized to pregabalin or placebo for the first period, and were then switched to the other treatment for the second period (2 weeks dose titration and 4 weeks fixed dose for each treatment period). There was a 2-week single-blind washout (blinded to participant) between the treatment periods. A 1-week taper was administered at the end of the second treatment period, followed by a final follow-up visit.
Measure Participants	198	186
Least Squares Mean (Standard Error) [units on a scale]	35.72 (1.44)	37.08 (1.46)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments	Analysis was done using a linear mixed effects model including baseline value, sequence, period, center, and treatment as fixed effect factors and participant within sequence and within-participant error as random factors.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.2854
	Comments	Secondary analysis was two-sided and performed at the 0.05 significance level. No corrections to alpha to control for potential inflation of Type I error resulting from multiple comparisons were made.
	Method	Linear mixed effects model
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.37
	Confidence Interval	(2-Sided) 95%; -3.88 to 1.15
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.27
	Estimation Comments

12. Secondary Outcome

Title	Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QOL-DN) Total Quality of Life (TQOL) Score Measured Over the Last 2 Weeks of Each Treatment Period (Week 6 of Each Treatment Period)
Description	Norfolk QOL-DN is a 35-item participant-rated questionnaire used to assess impact of diabetic neuropathy on the quality of life of participants with diabetic neuropathy. All symptoms (1 - 7) are scored as either 1 or 0, indicating presence or absence of the symptom. With the exception of questions 31 and 32, the other items are scored according to the 5-point Likert Scale (0 - 4, "no problem" to "severe problem"). In question 31, "good", the middle item, is scored as 0, "very good" as -1, "excellent" as -2, "fair" as 1, and "poor" as 2. In question 32, "about the same", the middle item, is scored as 0, "somewhat better" as -1, "much better" as -2, "somewhat worse" as 1, and "much worse" as 2. TQOL score should be summed as follow: sum (Σ) (1 - 7, 8 - 35). The scales and subscales are calculated without weighting of any kind, and reported as the integer sum of the listed questionnaire items.
Time Frame	End of Period (includes both Visits 6 and 11)

Outcome Measure Data

Analysis Population Description

All participants who were randomized, treated (ie, received at least one dose of study medication) and had at least one post-randomization efficacy evaluation were included in the ITT analysis (N: 203). This was the primary analysis set.

Arm/Group Title	Pregabalin	Placebo
Arm/Group Description	The below table included data from participants while receiving pregabalin in either period of the 2-period crossover study design. This crossover study consisted of two double blind 6-week treatment periods where participants were randomized to pregabalin or placebo for the first period, and were then switched to the other treatment for the second period (2 weeks dose titration and 4 weeks fixed dose for each treatment period). There was a 2-week single-blind washout (blinded to participant) between the treatment periods. A 1-week taper was administered at the end of the second treatment period, followed by a final follow-up visit.	The below table included data from participants while receiving placebo in either period of the 2-period crossover study design. This crossover study consisted of two double blind 6-week treatment periods where participants were randomized to pregabalin or placebo for the first period, and were then switched to the other treatment for the second period (2 weeks dose titration and 4 weeks fixed dose for each treatment period). There was a 2-week single-blind washout (blinded to participant) between the treatment periods. A 1-week taper was administered at the end of the second treatment period, followed by a final follow-up visit.
Measure Participants	198	186
Least Squares Mean (Standard Error) [units on a scale]	29.31 (1.17)	30.77 (1.19)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments	Analysis was done using a linear mixed effects model including baseline value, sequence, period, center, and treatment as fixed effect factors and participant within sequence and within-participant error as random factors.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.1805
	Comments	Secondary analysis was two-sided and performed at the 0.05 significance level. No corrections to alpha to control for potential inflation of Type I error resulting from multiple comparisons were made.
	Method	Linear mixed effects model
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.46
	Confidence Interval	(2-Sided) 95%; -3.60 to 0.68
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.09
	Estimation Comments

13. Secondary Outcome

Title	Norfolk QOL-DN Symptoms Domain Score Measured Over the Last 2 Weeks of Each Treatment Period (Week 6 of Each Treatment Period)
Description	Norfolk QOL-DN is a 35-item participant-rated questionnaire used to assess impact of diabetic neuropathy on the quality of life of participants with diabetic neuropathy. All symptoms (1 - 7) are scored as either 1 or 0, indicating presence or absence of the symptom. With the exception of questions 31 and 32, the other items are scored according to the 5-point Likert Scale (0 - 4, "no problem" to "severe problem"). In question 31, "good", the middle item, is scored as 0, "very good" as -1, "excellent" as -2, "fair" as 1, and "poor" as 2. In question 32, "about the same", the middle item, is scored as 0, "somewhat better" as -1, "much better" as -2, "somewhat worse" as 1, and "much worse" as 2. The symptoms domain score should be summed as follow: Σ(1 - 7, 9). The scales and subscales are calculated without weighting of any kind, and reported as the integer sum of the listed questionnaire items.
Time Frame	End of Period (includes both Visits 6 and 11)

Outcome Measure Data

Analysis Population Description

All participants who were randomized, treated (ie, received at least one dose of study medication) and had at least one post-randomization efficacy evaluation were included in the ITT analysis (N: 203). This was the primary analysis set.

Arm/Group Title	Pregabalin	Placebo
Arm/Group Description	The below table included data from participants while receiving pregabalin in either period of the 2-period crossover study design. This crossover study consisted of two double blind 6-week treatment periods where participants were randomized to pregabalin or placebo for the first period, and were then switched to the other treatment for the second period (2 weeks dose titration and 4 weeks fixed dose for each treatment period). There was a 2-week single-blind washout (blinded to participant) between the treatment periods. A 1-week taper was administered at the end of the second treatment period, followed by a final follow-up visit.	The below table included data from participants while receiving placebo in either period of the 2-period crossover study design. This crossover study consisted of two double blind 6-week treatment periods where participants were randomized to pregabalin or placebo for the first period, and were then switched to the other treatment for the second period (2 weeks dose titration and 4 weeks fixed dose for each treatment period). There was a 2-week single-blind washout (blinded to participant) between the treatment periods. A 1-week taper was administered at the end of the second treatment period, followed by a final follow-up visit.
Measure Participants	198	186
Least Squares Mean (Standard Error) [units on a scale]	7.65 (0.32)	7.99 (0.33)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments	Analysis was done using a linear mixed effects model including baseline value, sequence, period, center, and treatment as fixed effect factors and participant within sequence and within-participant error as random factors.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.3028
	Comments	Secondary analysis was two-sided and performed at the 0.05 significance level. No corrections to alpha to control for potential inflation of Type I error resulting from multiple comparisons were made.
	Method	Linear mixed effects model
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.34
	Confidence Interval	(2-Sided) 95%; -0.99 to 0.31
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.33
	Estimation Comments

14. Secondary Outcome

Title	Norfolk QOL-DN Activities of Daily Living Domain Score Measured Over the Last 2 Weeks of Each Treatment Period (Week 6 of Each Treatment Period)
Description	Norfolk QOL-DN is a 35-item participant-rated questionnaire used to assess impact of diabetic neuropathy on the quality of life of participants with diabetic neuropathy. All symptoms (1 - 7) are scored as either 1 or 0, indicating presence or absence of the symptom. With the exception of questions 31 and 32, the other items are scored according to the 5-point Likert Scale (0 - 4, "no problem" to "severe problem"). In question 31, "good", the middle item, is scored as 0, "very good" as -1, "excellent" as -2, "fair" as 1, and "poor" as 2. In question 32, "about the same", the middle item, is scored as 0, "somewhat better" as -1, "much better" as -2, "somewhat worse" as 1, and "much worse" as 2. The activities of daily living domain score should be summed as follow: Σ(12, 22, 23, 25, 26). The scales and subscales are calculated without weighting of any kind, and reported as the integer sum of the listed questionnaire items.
Time Frame	End of Period (includes both Visits 6 and 11)

Outcome Measure Data

Analysis Population Description

All participants who were randomized, treated (ie, received at least one dose of study medication) and had at least one post-randomization efficacy evaluation were included in the ITT analysis (N: 203). This was the primary analysis set.

Arm/Group Title	Pregabalin	Placebo
Arm/Group Description	The below table included data from participants while receiving pregabalin in either period of the 2-period crossover study design. This crossover study consisted of two double blind 6-week treatment periods where participants were randomized to pregabalin or placebo for the first period, and were then switched to the other treatment for the second period (2 weeks dose titration and 4 weeks fixed dose for each treatment period). There was a 2-week single-blind washout (blinded to participant) between the treatment periods. A 1-week taper was administered at the end of the second treatment period, followed by a final follow-up visit.	The below table included data from participants while receiving placebo in either period of the 2-period crossover study design. This crossover study consisted of two double blind 6-week treatment periods where participants were randomized to pregabalin or placebo for the first period, and were then switched to the other treatment for the second period (2 weeks dose titration and 4 weeks fixed dose for each treatment period). There was a 2-week single-blind washout (blinded to participant) between the treatment periods. A 1-week taper was administered at the end of the second treatment period, followed by a final follow-up visit.
Measure Participants	198	186
Least Squares Mean (Standard Error) [units on a scale]	2.36 (0.19)	2.42 (0.20)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments	Analysis was done using a linear mixed effects model including baseline value, sequence, period, center, and treatment as fixed effect factors and participant within sequence and within-participant error as random factors.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.7542
	Comments	Secondary analysis was two-sided and performed at the 0.05 significance level. No corrections to alpha to control for potential inflation of Type I error resulting from multiple comparisons were made.
	Method	Linear mixed effects model
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.06
	Confidence Interval	(2-Sided) 95%; -0.41 to 0.30
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.18
	Estimation Comments

15. Secondary Outcome

Title	Norfolk QOL-DN Physical Functioning / Large Fiber Domain Score Measured Over the Last 2 Weeks of Each Treatment Period (Week 6 of Each Treatment Period)
Description	Norfolk QOL-DN is a 35-item participant-rated questionnaire used to assess impact of diabetic neuropathy on the quality of life of participants with diabetic neuropathy. All symptoms (1 - 7) are scored as either 1 or 0, indicating presence or absence of the symptom. With the exception of questions 31 and 32, the other items are scored according to the 5-point Likert Scale (0 - 4, "no problem" to "severe problem"). In question 31, "good", the middle item, is scored as 0, "very good" as -1, "excellent" as -2, "fair" as 1, and "poor" as 2. In question 32, "about the same", the middle item, is scored as 0, "somewhat better" as -1, "much better" as -2, "somewhat worse" as 1, and "much worse" as 2. The physical functioning / large fiber domain score should be summed as follow: Σ(8, 11, 13 - 15, 24, 27 - 35). The scales and subscales are calculated without weighting of any kind, and reported as the integer sum of the listed questionnaire items.
Time Frame	End of Period (includes both Visits 6 and 11)

Outcome Measure Data

Analysis Population Description

All participants who were randomized, treated (ie, received at least one dose of study medication) and had at least one post-randomization efficacy evaluation were included in the ITT analysis (N: 203). This was the primary analysis set.

Arm/Group Title	Pregabalin	Placebo
Arm/Group Description	The below table included data from participants while receiving pregabalin in either period of the 2-period crossover study design. This crossover study consisted of two double blind 6-week treatment periods where participants were randomized to pregabalin or placebo for the first period, and were then switched to the other treatment for the second period (2 weeks dose titration and 4 weeks fixed dose for each treatment period). There was a 2-week single-blind washout (blinded to participant) between the treatment periods. A 1-week taper was administered at the end of the second treatment period, followed by a final follow-up visit.	The below table included data from participants while receiving placebo in either period of the 2-period crossover study design. This crossover study consisted of two double blind 6-week treatment periods where participants were randomized to pregabalin or placebo for the first period, and were then switched to the other treatment for the second period (2 weeks dose titration and 4 weeks fixed dose for each treatment period). There was a 2-week single-blind washout (blinded to participant) between the treatment periods. A 1-week taper was administered at the end of the second treatment period, followed by a final follow-up visit.
Measure Participants	198	186
Least Squares Mean (Standard Error) [units on a scale]	15.51 (0.73)	16.78 (0.75)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments	Analysis was done using a linear mixed effects model including baseline value, sequence, period, center, and treatment as fixed effect factors and participant within sequence and within-participant error as random factors.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0634
	Comments	Secondary analysis was two-sided and performed at the 0.05 significance level. No corrections to alpha to control for potential inflation of Type I error resulting from multiple comparisons were made.
	Method	Linear mixed effects model
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.27
	Confidence Interval	(2-Sided) 95%; -2.62 to 0.07
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.68
	Estimation Comments

16. Secondary Outcome

Title	Norfolk QOL-DN Small Fiber Domain Score Measured Over the Last 2 Weeks of Each Treatment Period (Week 6 of Each Treatment Period)
Description	Norfolk QOL-DN is a 35-item participant-rated questionnaire used to assess impact of diabetic neuropathy on the quality of life of participants with diabetic neuropathy. All symptoms (1 - 7) are scored as either 1 or 0, indicating presence or absence of the symptom. With the exception of questions 31 and 32, the other items are scored according to the 5-point Likert Scale (0 - 4, "no problem" to "severe problem"). In question 31, "good", the middle item, is scored as 0, "very good" as -1, "excellent" as -2, "fair" as 1, and "poor" as 2. In question 32, "about the same", the middle item, is scored as 0, "somewhat better" as -1, "much better" as -2, "somewhat worse" as 1, and "much worse" as 2. The small fiber domain score should be summed as follow: Σ(10, 16, 17, 18). The scales and subscales are calculated without weighting of any kind, and reported as the integer sum of the listed questionnaire items.
Time Frame	End of Period (includes both Visits 6 and 11)

Outcome Measure Data

Analysis Population Description

All participants who were randomized, treated (ie, received at least one dose of study medication) and had at least one post-randomization efficacy evaluation were included in the ITT analysis (N: 203). This was the primary analysis set.

Arm/Group Title	Pregabalin	Placebo
Arm/Group Description	The below table included data from participants while receiving pregabalin in either period of the 2-period crossover study design. This crossover study consisted of two double blind 6-week treatment periods where participants were randomized to pregabalin or placebo for the first period, and were then switched to the other treatment for the second period (2 weeks dose titration and 4 weeks fixed dose for each treatment period). There was a 2-week single-blind washout (blinded to participant) between the treatment periods. A 1-week taper was administered at the end of the second treatment period, followed by a final follow-up visit.	The below table included data from participants while receiving placebo in either period of the 2-period crossover study design. This crossover study consisted of two double blind 6-week treatment periods where participants were randomized to pregabalin or placebo for the first period, and were then switched to the other treatment for the second period (2 weeks dose titration and 4 weeks fixed dose for each treatment period). There was a 2-week single-blind washout (blinded to participant) between the treatment periods. A 1-week taper was administered at the end of the second treatment period, followed by a final follow-up visit.
Measure Participants	198	186
Least Squares Mean (Standard Error) [units on a scale]	2.77 (0.17)	2.53 (0.17)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments	Analysis was done using a linear mixed effects model including baseline value, sequence, period, center, and treatment as fixed effect factors and participant within sequence and within-participant error as random factors.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.1985
	Comments	Secondary analysis was two-sided and performed at the 0.05 significance level. No corrections to alpha to control for potential inflation of Type I error resulting from multiple comparisons were made.
	Method	Linear mixed effects model
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.24
	Confidence Interval	(2-Sided) 95%; -0.13 to 0.62
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.19
	Estimation Comments

17. Secondary Outcome

Title	Norfolk QOL-DN Autonomic Domain Score Measured Over the Last 2 Weeks of Each Treatment Period (Week 6 of Each Treatment Period)
Description	Norfolk QOL-DN is a 35-item participant-rated questionnaire used to assess impact of diabetic neuropathy on the quality of life of participants with diabetic neuropathy. All symptoms (1 - 7) are scored as either 1 or 0, indicating presence or absence of the symptom. With the exception of questions 31 and 32, the other items are scored according to the 5-point Likert Scale (0 - 4, "no problem" to "severe problem"). In question 31, "good", the middle item, is scored as 0, "very good" as -1, "excellent" as -2, "fair" as 1, and "poor" as 2. In question 32, "about the same", the middle item, is scored as 0, "somewhat better" as -1, "much better" as -2, "somewhat worse" as 1, and "much worse" as 2. The autonomic domain score should be summed as follow: Σ(19, 20, 21). The scales and subscales are calculated without weighting of any kind, and reported as the integer sum of the listed questionnaire items.
Time Frame	End of Period (includes both Visits 6 and 11)

Outcome Measure Data

Analysis Population Description

All participants who were randomized, treated (ie, received at least one dose of study medication) and had at least one post-randomization efficacy evaluation were included in the ITT analysis (N: 203). This was the primary analysis set.

Arm/Group Title	Pregabalin	Placebo
Arm/Group Description	The below table included data from participants while receiving pregabalin in either period of the 2-period crossover study design. This crossover study consisted of two double blind 6-week treatment periods where participants were randomized to pregabalin or placebo for the first period, and were then switched to the other treatment for the second period (2 weeks dose titration and 4 weeks fixed dose for each treatment period). There was a 2-week single-blind washout (blinded to participant) between the treatment periods. A 1-week taper was administered at the end of the second treatment period, followed by a final follow-up visit.	The below table included data from participants while receiving placebo in either period of the 2-period crossover study design. This crossover study consisted of two double blind 6-week treatment periods where participants were randomized to pregabalin or placebo for the first period, and were then switched to the other treatment for the second period (2 weeks dose titration and 4 weeks fixed dose for each treatment period). There was a 2-week single-blind washout (blinded to participant) between the treatment periods. A 1-week taper was administered at the end of the second treatment period, followed by a final follow-up visit.
Measure Participants	198	186
Least Squares Mean (Standard Error) [units on a scale]	1.07 (0.10)	1.08 (0.10)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments	Analysis was done using a linear mixed effects model including baseline value, sequence, period, center, and treatment as fixed effect factors and participant within sequence and within-participant error as random factors.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.9686
	Comments	Secondary analysis was two-sided and performed at the 0.05 significance level. No corrections to alpha to control for potential inflation of Type I error resulting from multiple comparisons were made.
	Method	Linear mixed effects model
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.00
	Confidence Interval	(2-Sided) 95%; -0.21 to 0.20
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.10
	Estimation Comments

18. Secondary Outcome

Title	Percentage of Participants With Patient Global Impression of Change (PGIC) Score From Baseline at the End of Period 1 (Week 6)
Description	The PGIC is a participant-rated instrument that measures the participant's assessment of change in his/her overall status on a scale ranging from 1 (very much improved) to 7 (very much worse). Original scores (OS; 7 different scores) and categorized scores (CS; 4 different scores) were provided. Categorized scores were very much improved (consisting of very much improved and much improved); any improvement (consisting of very much improved, much improved, and minimally improved); no change (consisting of no change); and any worsening (consisting of minimally worse, much worse, and very much worse). Due to the crossover design, PGIC was analyzed at the end of period 1 (V6).
Time Frame	End of Period 1 (V6)

Outcome Measure Data

Analysis Population Description

All participants who were randomized, treated (ie, received at least one dose of study medication) and had at least one post-randomization efficacy evaluation were included in the ITT analysis (N: 203). This was the primary analysis set. Numbers of participants analyzed are provided in section Measured Values in brackets (N: Pregabalin, Placebo).

Arm/Group Title	Pregabalin	Placebo
Arm/Group Description	The below table included data from participants while receiving pregabalin in either period of the 2-period crossover study design. This crossover study consisted of two double blind 6-week treatment periods where participants were randomized to pregabalin or placebo for the first period, and were then switched to the other treatment for the second period (2 weeks dose titration and 4 weeks fixed dose for each treatment period). There was a 2-week single-blind washout (blinded to participant) between the treatment periods. A 1-week taper was administered at the end of the second treatment period, followed by a final follow-up visit.	The below table included data from participants while receiving placebo in either period of the 2-period crossover study design. This crossover study consisted of two double blind 6-week treatment periods where participants were randomized to pregabalin or placebo for the first period, and were then switched to the other treatment for the second period (2 weeks dose titration and 4 weeks fixed dose for each treatment period). There was a 2-week single-blind washout (blinded to participant) between the treatment periods. A 1-week taper was administered at the end of the second treatment period, followed by a final follow-up visit.
Measure Participants	98	102
OS: Very much improved	11.2 11.1%	5.9 5.8%
OS: Much improved	39.8 39.4%	25.5 25%
OS: Minimally improved	30.6 30.3%	27.5 27%
OS: No change	13.3 13.2%	33.3 32.6%
OS: Minimally worse	2.0 2%	5.9 5.8%
OS: Much worse	2.0 2%	1.0 1%
OS: Very much worse	1.0 1%	1.0 1%
CS: Very much improved	51.0 50.5%	31.4 30.8%
CS: Any improvement	81.6 80.8%	58.8 57.6%
CS: No change	13.3 13.2%	33.3 32.6%
CS: Any worsening	5.1 5%	7.8 7.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments	Odds ratio is based on the binary response for any improvement while p-value is from the comparison of the original scale of 7 possible outcomes. P-value was calculated by using Cochran Mantel-Haenszel (CMH) test. PGIC values at the end of Period 1 data was compared between treatment groups.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0020
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.5400
	Confidence Interval	(2-Sided) 95%; 1.30 to 4.95
	Parameter Dispersion	Type: Value:
	Estimation Comments

19. Secondary Outcome

Title	Mean Sleep Interference Rating Score at the End of Each Treatment Period (Week 6 of Each Treatment Period)
Description	The daily sleep diary consists of an 11-point numeric rating scale with which the participant rates how painful DPN pain has interfered with their sleep during the past 24 hours. Zero indicates "does not interfere with sleep" and 10 indicates "completely interferes (unable to sleep due to pain)". Self-assessment was performed daily in the evening before bedtime on a telephone via IVRS (time window for completion between 6.00 pm to midnight) after completion of the daily pain diary.
Time Frame	End of Period (includes both Visits 6 and 11)

Outcome Measure Data

Analysis Population Description

All participants who were randomized, treated (ie, received at least one dose of study medication) and had at least one post-randomization efficacy evaluation were included in the ITT analysis (N: 203). This was the primary analysis set.

Arm/Group Title	Pregabalin	Placebo
Arm/Group Description	The below table included data from participants while receiving pregabalin in either period of the 2-period crossover study design. This crossover study consisted of two double blind 6-week treatment periods where participants were randomized to pregabalin or placebo for the first period, and were then switched to the other treatment for the second period (2 weeks dose titration and 4 weeks fixed dose for each treatment period). There was a 2-week single-blind washout (blinded to participant) between the treatment periods. A 1-week taper was administered at the end of the second treatment period, followed by a final follow-up visit.	The below table included data from participants while receiving placebo in either period of the 2-period crossover study design. This crossover study consisted of two double blind 6-week treatment periods where participants were randomized to pregabalin or placebo for the first period, and were then switched to the other treatment for the second period (2 weeks dose titration and 4 weeks fixed dose for each treatment period). There was a 2-week single-blind washout (blinded to participant) between the treatment periods. A 1-week taper was administered at the end of the second treatment period, followed by a final follow-up visit.
Measure Participants	198	186
Least Squares Mean (Standard Error) [units on a scale]	3.66 (0.12)	4.05 (0.13)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments	Analysis was done using a linear mixed effects model including baseline value, sequence, period, center, and treatment as fixed effect factors and participant within sequence and within-participant error as random factors. LOCF approach was applied.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0105
	Comments	Secondary analysis was two-sided and performed at the 0.05 significance level. No corrections to alpha to control for potential inflation of Type I error resulting from multiple comparisons were made.
	Method	Linear mixed effects model
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.38
	Confidence Interval	(2-Sided) 95%; -0.68 to -0.09
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.15
	Estimation Comments

20. Secondary Outcome

Title	Hospital Anxiety and Depression Scale - Anxiety (HADS-A) Total Score at the End of Each Treatment Period (Week 6 of Each Treatment Period)
Description	The Hospital Anxiety and Depression Scale (HADS) is a 14-item self-administered questionnaire that consists of 2 scales, one measuring anxiety (HADS-A), and the other measuring depression (HADS-D). Each subscale consists of 7 statements and the participant responds as to how each item applies to him/her over the past week on 4-point response scale. Separate scores are calculated for anxiety and depression and a score (ranging from 0 to 21) is obtained for each subscale. The higher the score, the more severe the anxiety or depression.
Time Frame	End of Period (includes both Visits 6 and 11)

Outcome Measure Data

Analysis Population Description

All participants who were randomized, treated (ie, received at least one dose of study medication) and had at least one post-randomization efficacy evaluation were included in the ITT analysis (N: 203). This was the primary analysis set.

Arm/Group Title	Pregabalin	Placebo
Arm/Group Description	The below table included data from participants while receiving pregabalin in either period of the 2-period crossover study design. This crossover study consisted of two double blind 6-week treatment periods where participants were randomized to pregabalin or placebo for the first period, and were then switched to the other treatment for the second period (2 weeks dose titration and 4 weeks fixed dose for each treatment period). There was a 2-week single-blind washout (blinded to participant) between the treatment periods. A 1-week taper was administered at the end of the second treatment period, followed by a final follow-up visit.	The below table included data from participants while receiving placebo in either period of the 2-period crossover study design. This crossover study consisted of two double blind 6-week treatment periods where participants were randomized to pregabalin or placebo for the first period, and were then switched to the other treatment for the second period (2 weeks dose titration and 4 weeks fixed dose for each treatment period). There was a 2-week single-blind washout (blinded to participant) between the treatment periods. A 1-week taper was administered at the end of the second treatment period, followed by a final follow-up visit.
Measure Participants	198	186
Least Squares Mean (Standard Error) [units on a scale]	4.65 (0.19)	4.92 (0.20)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments	Analysis was done using a linear mixed effects model including baseline value, sequence, period, center, and treatment as fixed effect factors and participant within sequence and within-participant error as random factors.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.1178
	Comments	Secondary analysis was two-sided and performed at the 0.05 significance level. No corrections to alpha to control for potential inflation of Type I error resulting from multiple comparisons were made.
	Method	Linear mixed effects model
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.28
	Confidence Interval	(2-Sided) 95%; -0.63 to 0.07
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.18
	Estimation Comments

21. Secondary Outcome

Title	Hospital Anxiety and Depression Scale - Depression (HADS-D) Total Score at the End of Each Treatment Period (Week 6 of Each Treatment Period)
Description	The HADS is a 14-item self-administered questionnaire that consists of 2 scales, one measuring anxiety (HADS-A), and the other measuring depression (HADS-D). Each subscale consists of 7 statements and the participant responds as to how each item applies to him/her over the past week on 4-point response scale. Separate scores are calculated for anxiety and depression and a score (ranging from 0 to 21) is obtained for each subscale. The higher the score, the more severe the anxiety or depression.
Time Frame	End of Period (includes both Visits 6 and 11)

Outcome Measure Data

Analysis Population Description

All participants who were randomized, treated (ie, received at least one dose of study medication) and had at least one post-randomization efficacy evaluation were included in the ITT analysis (N: 203). This was the primary analysis set.

Arm/Group Title	Pregabalin	Placebo
Arm/Group Description	The below table included data from participants while receiving pregabalin in either period of the 2-period crossover study design. This crossover study consisted of two double blind 6-week treatment periods where participants were randomized to pregabalin or placebo for the first period, and were then switched to the other treatment for the second period (2 weeks dose titration and 4 weeks fixed dose for each treatment period). There was a 2-week single-blind washout (blinded to participant) between the treatment periods. A 1-week taper was administered at the end of the second treatment period, followed by a final follow-up visit.	The below table included data from participants while receiving placebo in either period of the 2-period crossover study design. This crossover study consisted of two double blind 6-week treatment periods where participants were randomized to pregabalin or placebo for the first period, and were then switched to the other treatment for the second period (2 weeks dose titration and 4 weeks fixed dose for each treatment period). There was a 2-week single-blind washout (blinded to participant) between the treatment periods. A 1-week taper was administered at the end of the second treatment period, followed by a final follow-up visit.
Measure Participants	198	186
Least Squares Mean (Standard Error) [units on a scale]	3.73 (0.20)	3.97 (0.20)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments	Analysis was done using a linear mixed effects model including baseline value, sequence, period, center, and treatment as fixed effect factors and participant within sequence and within-participant error as random factors.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.1990
	Comments	Secondary analysis was two-sided and performed at the 0.05 significance level. No corrections to alpha to control for potential inflation of Type I error resulting from multiple comparisons were made.
	Method	Linear mixed effects model
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.24
	Confidence Interval	(2-Sided) 95%; -0.60 to 0.13
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.18
	Estimation Comments

22. Secondary Outcome

Title	Euro QoL-5 Dimensions (EQ-5D) - Health State Profile Utility Scores at the End of Each Treatment Period (Week 6 of Each Treatment Period)
Description	The EQ-5D describes participant's health status based on 5 attributes producing an 5 digit index score. The 5 dimensions are: mobility, self-care, usual activities, pain / discomfort, and anxiety / depression. Dolan 1997 advised how to transfer this index score to a single score for clinical trials, a revised single index was published in 2001. The index uses general population weighted estimates for various health states. In general, the range of the single index tends to vary between 0 = death and 1 = perfect health and there are some states that have been rated by the general population to be worse than death which may result in numbers below 0.
Time Frame	End of Period (includes both Visits 6 and 11)

Outcome Measure Data

Analysis Population Description

All participants who were randomized, treated (ie, received at least one dose of study medication) and had at least one post-randomization efficacy evaluation were included in the ITT analysis (N: 203). This was the primary analysis set.

Arm/Group Title	Pregabalin	Placebo
Arm/Group Description	The below table included data from participants while receiving pregabalin in either period of the 2-period crossover study design. This crossover study consisted of two double blind 6-week treatment periods where participants were randomized to pregabalin or placebo for the first period, and were then switched to the other treatment for the second period (2 weeks dose titration and 4 weeks fixed dose for each treatment period). There was a 2-week single-blind washout (blinded to participant) between the treatment periods. A 1-week taper was administered at the end of the second treatment period, followed by a final follow-up visit.	The below table included data from participants while receiving placebo in either period of the 2-period crossover study design. This crossover study consisted of two double blind 6-week treatment periods where participants were randomized to pregabalin or placebo for the first period, and were then switched to the other treatment for the second period (2 weeks dose titration and 4 weeks fixed dose for each treatment period). There was a 2-week single-blind washout (blinded to participant) between the treatment periods. A 1-week taper was administered at the end of the second treatment period, followed by a final follow-up visit.
Measure Participants	198	186
Index score Dolan 1997	0.649 (0.015)	0.643 (0.015)
Index score Dolan 2001	0.650 (0.014)	0.641 (0.014)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments	Statistical analysis presented above is for the Index score Dolan 1997. Analysis was done using a linear mixed effects model including baseline value, sequence, period, center, and treatment as fixed effect factors and participant within sequence and within-participant error as random factors.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.71107
	Comments	Secondary analysis was two-sided and performed at the 0.05 significance level. No corrections to alpha to control for potential inflation of Type I error resulting from multiple comparisons were made.
	Method	Linear mixed effects model
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.006
	Confidence Interval	(2-Sided) 95%; -0.025 to 0.037
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.02
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Pregabalin, Placebo
	Comments	Statistical analysis presented above is for the Index score Dolan 2001. Analysis was done using a linear mixed effects model including baseline value, sequence, period, center, and treatment as fixed effect factors and participant within sequence and within-participant error as random factors.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.53965
	Comments	Secondary analysis was two-sided and performed at the 0.05 significance level. No corrections to alpha to control for potential inflation of Type I error resulting from multiple comparisons were made.
	Method	Linear mixed effects model
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.009
	Confidence Interval	(2-Sided) 95%; -0.021 to 0.039
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.02
	Estimation Comments

Adverse Events

Time Frame	From the time that the participants were provided the informed consent document through and including 28 calendar days after the last administration of the study drug.
Adverse Event Reporting Description	The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Arm/Group Title	Pregabalin		Placebo
Arm/Group Description	The below table included data from participants while receiving pregabalin in either period of the 2-period crossover study design. This crossover study consisted of two double blind 6-week treatment periods where participants were randomized to pregabalin or placebo for the first period, and were then switched to the other treatment for the second period (2 weeks dose titration and 4 weeks fixed dose for each treatment period). There was a 2-week single-blind washout (blinded to participant) between the treatment periods. A 1-week taper was administered at the end of the second treatment period, followed by a final follow-up visit.		The below table included data from participants while receiving placebo in either period of the 2-period crossover study design. This crossover study consisted of two double blind 6-week treatment periods where participants were randomized to pregabalin or placebo for the first period, and were then switched to the other treatment for the second period (2 weeks dose titration and 4 weeks fixed dose for each treatment period). There was a 2-week single-blind washout (blinded to participant) between the treatment periods. A 1-week taper was administered at the end of the second treatment period, followed by a final follow-up visit.
All Cause Mortality
	Pregabalin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Pregabalin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/198 (4.5%)		2/186 (1.1%)
Cardiac disorders
Angina unstable	1/198 (0.5%)		0/186 (0%)
Endocrine disorders
Myocardial infarction	1/198 (0.5%)		0/186 (0%)
Infections and infestations
Cellulitis	1/198 (0.5%)		0/186 (0%)
Diverticulitis	1/198 (0.5%)		0/186 (0%)
Urinary tract infection	0/198 (0%)		1/186 (0.5%)
Urosepsis	1/198 (0.5%)		0/186 (0%)
Metabolism and nutrition disorders
Hypoglycaemia	1/198 (0.5%)		0/186 (0%)
Musculoskeletal and connective tissue disorders
Back pain	1/198 (0.5%)		0/186 (0%)
Muscular weakness	1/198 (0.5%)		0/186 (0%)
Nervous system disorders
Cerebral ischaemia	1/198 (0.5%)		0/186 (0%)
Drug withdrawal convulsions	1/198 (0.5%)		0/186 (0%)
Surgical and medical procedures
Fracture treatment	1/198 (0.5%)		0/186 (0%)
Vascular disorders
Deep vein thrombosis	0/198 (0%)		1/186 (0.5%)
Other (Not Including Serious) Adverse Events
	Pregabalin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	53/198 (26.8%)		38/186 (20.4%)
Eye disorders
Vision blurred	4/198 (2%)		1/186 (0.5%)
Gastrointestinal disorders
Constipation	3/198 (1.5%)		4/186 (2.2%)
Diarrhoea	2/198 (1%)		5/186 (2.7%)
Dry mouth	5/198 (2.5%)		1/186 (0.5%)
Nausea	5/198 (2.5%)		6/186 (3.2%)
General disorders
Fatigue	11/198 (5.6%)		3/186 (1.6%)
Oedema peripheral	9/198 (4.5%)		2/186 (1.1%)
Infections and infestations
Upper respiratory tract infection	5/198 (2.5%)		8/186 (4.3%)
Investigations
Weight increased	5/198 (2.5%)		1/186 (0.5%)
Musculoskeletal and connective tissue disorders
Back pain	4/198 (2%)		1/186 (0.5%)
Nervous system disorders
Dizziness	11/198 (5.6%)		6/186 (3.2%)
Headache	5/198 (2.5%)		8/186 (4.3%)
Somnolence	12/198 (6.1%)		4/186 (2.2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.